Needle for fundus injection and preparation method thereof

Abstract

The invention relates to the technical field of medical equipment, in particular to a fundus injection needle and a preparation method thereof.The preparation method comprises the following steps that after an injection needle body is subjected to surface modification through a silane coupling agent, the injection needle body is subjected to a first soaking reaction in an acrylic acid modified poly-beta-serine aqueous solution at the temperature of 50-70 DEG C, and then the injection needle body is subjected to a second soaking reaction at the temperature of 50-70 DEG C; and carrying out a second soaking reaction in a toluene solution of bromobutane at 70-90 DEG C to obtain the fundus injection needle. According to the preparation method of the eye fundus injection needle, poly-beta-serine and butyl are grafted to the surface of the injection needle body at the same time through the silane coupling agent to achieve surface modification of the injection needle body, so that the modified eye fundus injection needle has excellent biocompatibility, the treatment effect of eye fundus injection is improved, and the eye fundus injection needle has good application prospects. The comfort of the patient is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of medical equipment, and in particular to a needle for fundus injection and a preparation method thereof. Background Art

[0002] Intraocular injection is currently the main method for treating various blinding fundus diseases such as wet age-related macular degeneration, diabetic macular edema, central retinal vein occlusion, choroidal neovascularization, etc. However, this treatment method requires multiple treatments and long-term follow-up.

[0003] Intraocular injections usually show improvement in visual function within a few weeks of injection. However, this treatment also has certain risks and side effects, such as the poor biocompatibility of the injection needle, which can easily cause allergies and discomfort to patients.

[0004] In view of this, how to improve the biocompatibility of injection needles is a technical problem that needs to be solved urgently. Summary of the invention

[0005] In order to solve the problem of poor biocompatibility of injection needles in the prior art, the present invention provides a method for preparing a fundus injection needle. The preparation method modifies the surface of the injection needle body by modifying poly-β-serine with acrylic acid, so that the modified injection needle has excellent biocompatibility, improves the therapeutic effect of fundus injection, and solves the problem of poor biocompatibility of injection needles in the prior art.

[0006] The technical solution adopted by the present invention to solve its technical problem is: A method for preparing a fundus injection needle comprises the following steps: after surface modification of an injection needle body by a silane coupling agent, a first soaking reaction is carried out in an acrylic acid-modified poly-β-serine aqueous solution at 50-70° C., and then a second soaking reaction is carried out in a toluene solution of butyl bromide at 70-90° C. to obtain the fundus injection needle.

[0007] Optionally, the acrylic acid-modified poly-β-serine is prepared according to the following method: S21: mixing poly-β-serine, triethylamine and anhydrous tetrahydrofuran to obtain a first reaction solution; S22: mixing acryloyl chloride and anhydrous tetrahydrofuran to obtain a second reaction solution; S23: adding the second reaction solution dropwise to the first reaction solution at 0° C. under an inert atmosphere, and reflux the reaction to obtain a reaction mixture; S24: adding the reaction mixture into ethanol, filtering, precipitating, and washing to obtain acrylic acid-modified poly-β-serine.

[0008] Optionally, the molar ratio of the poly-β-serine to the acryloyl chloride is 1:(1-3).

[0009] Optionally, surface modification of the injection needle body by a silane coupling agent comprises: S11: After mixing the silane coupling agent and the solvent, an acidic substance is added, and the pH value is adjusted to 5 to obtain a silane coupling agent solution; S12: placing the injection needle body in the silane coupling agent solution for ultrasonic treatment, and then drying to obtain a surface-modified injection needle.

[0010] Optionally, the silane coupling agent is KH550.

[0011] Optionally, the solvent in step S101 is a mixed solvent consisting of ethanol and deionized water.

[0012] Optionally, the injection needle body is made of stainless steel or polyimide.

[0013] Optionally, when the injection needle body is made of stainless steel, before surface modification of the injection needle body is performed using a silane coupling agent, the injection needle body is pretreated according to the following method: S21: soaking the injection needle body in HCl, and then ultrasonically treating it in an ethanol bath to obtain an E-stainless steel microneedle; S22: Anodizing the E-stainless steel microneedle in an ethylene glycol-based electrolyte to obtain an anodized stainless steel microneedle, which is recorded as EA-stainless steel microneedle; S23: heat-treating the EA-stainless steel microneedle at 500° C. in an inert gas atmosphere to obtain a pre-treated injection needle body.

[0014] Optionally, when the injection needle body is made of polyimide, before the surface of the injection needle body is modified by a silane coupling agent, the injection needle body is pretreated according to the following method: the injection needle body is pretreated with a NaOH solution at room temperature, rinsed, and dried to obtain a pretreated injection needle body.

[0015] Another object of the present invention is to provide a needle for fundus injection, which is prepared by the method for preparing the needle for fundus injection as described above.

[0016] The beneficial effects of the present invention are: The preparation method of the fundus injection needle provided by the present invention realizes surface modification of the injection needle body by simultaneously grafting poly-β-serine and butyl group onto the surface of the injection needle body through a silane coupling agent, so that the modified fundus injection needle has excellent biocompatibility, improves the therapeutic effect of fundus injection, and improves the comfort of patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The present invention is further described below in conjunction with the accompanying drawings and embodiments.

[0018] Figure 1 It is a schematic diagram of the process of modifying the injection needle body by the silane coupling agent in the present invention. DETAILED DESCRIPTION

[0019] The present invention is now further described in detail. The embodiments described below are exemplary and intended to be used to explain the present invention, but cannot be understood as limiting the present invention. All other embodiments obtained by ordinary technicians in this field without creative work based on the embodiments of the present invention belong to the scope of protection of the present invention.

[0020] In order to solve the problem of poor biocompatibility of injection needles in the prior art, the present invention provides a method for preparing a fundus injection needle, which comprises the following steps: after surface modification of the injection needle body by a silane coupling agent, a first immersion reaction is carried out in an acrylic acid-modified poly-β-serine aqueous solution at 50-70° C., and then a second immersion reaction is carried out in a toluene solution of butyl bromide at 70-90° C. to obtain the fundus injection needle.

[0021] The injection needle body refers to an existing injection needle that has not been surface-modified; the injection needle body can be prepared by any existing method; the present invention does not limit the preparation method of the injection needle body.

[0022] In the preparation method, the surface of the injection needle body is first modified by a silane coupling agent, so that the silane coupling agent reacts with the hydroxyl groups on the surface of the injection body and is bonded to the surface of the injection body by a silicon-oxygen bond. The preparation process is as follows: Figure 1 shown.

[0023] Then, the poly-β-serine and the butyl group are connected to the surface of the injection needle body through a silane coupling agent by soaking in an acrylic acid-modified poly-β-serine aqueous solution and a bromobutyl toluene solution in turn, thereby achieving modification of the injection needle body. The preparation process is shown in the following formula: .

[0024] Specifically, the preparation method of the fundus injection needle can be carried out according to the following steps: S1: surface-modifying the injection needle body by using a silane coupling agent to obtain an injection needle body modified by the silane coupling agent; S2: Preparation of acrylic acid-modified poly-β-serine; S3: The injection needle body modified by the silane coupling agent is immersed in an aqueous solution of acrylic acid-modified poly-β-serine for a first reaction at 50-70° C., and then immersed in a toluene solution of butyl bromide for a second reaction at 70-90° C. to obtain a needle for fundus injection.

[0025] The preparation method of the fundus injection needle provided by the present invention realizes surface modification of the injection needle body by simultaneously grafting poly-β-serine and butyl group onto the surface of the injection needle body through a silane coupling agent, so that the modified fundus injection needle has excellent biocompatibility, improves the therapeutic effect of fundus injection, and improves the comfort of patients.

[0026] Moreover, by introducing poly-β-serine and butyl, the surface of the fundus injection needle can effectively resist the adsorption of various proteins, reduce the risk of serum contamination, resist the adsorption of cells, platelets and various microorganisms, and have good antibacterial properties. While improving the therapeutic effect of fundus injection, it also helps to promote the recycling and secondary use of fundus injection needles, extend their service life and reduce costs.

[0027] In the present invention, the mass concentration range of acrylic acid-modified poly-β-serine in the acrylic acid-modified poly-β-serine aqueous solution is preferably (5-15)%; the mass concentration range of butyl bromide in the toluene solution of butyl bromide is preferably (10-30)%.

[0028] The preferred acrylic acid-modified poly-β-serine of the present invention is prepared according to the following method: S21: mixing poly-β-serine, triethylamine and anhydrous tetrahydrofuran to obtain a first reaction solution; S22: mixing acryloyl chloride and anhydrous tetrahydrofuran to obtain a second reaction solution; S23: adding the second reaction solution dropwise to the first reaction solution at 0° C. under an inert atmosphere, and refluxing the reaction, preferably refluxing for 24 hours, to obtain a reaction mixture; S24: adding the reaction mixture into ethanol, filtering, precipitating, and washing, preferably washing with ethanol three times, to obtain acrylic acid-modified poly-β-serine.

[0029] The preparation process of acrylic acid-modified poly-β-serine is shown in the following formula: ; Wherein, n is a natural number greater than 1.

[0030] In the present invention, the molar ratio of poly-β-serine to acryloyl chloride is preferably 1:(1-3).

[0031] The present invention reacts acryloyl chloride with poly-β-serine so that the prepared acrylic acid-modified poly-β-serine contains double bonds, and the poly-β-serine is grafted to the surface of the injection needle body through the double bonds, thereby improving the biocompatibility of the fundus injection needle, and at the same time enabling the surface of the fundus injection needle to effectively resist the adsorption of multiple proteins, reduce the risk of serum contamination, and resist the adsorption of cells, platelets and multiple microorganisms.

[0032] In order to facilitate the grafting of poly-β-serine onto the surface of the injection needle body, the present invention preferably uses a silane coupling agent to modify the surface of the injection needle body, including: S11: mixing a silane coupling agent with a solvent, preferably the mass ratio of the silane coupling agent to the solvent is 1:(10-20), adding an acidic substance, preferably acetic acid, and adjusting the pH value to 5 to facilitate the hydrolysis reaction of silane coupling, thereby obtaining a silane coupling agent solution; S12: placing the injection needle body in a silane coupling agent solution for ultrasonic treatment, and then drying to obtain a surface-modified injection needle.

[0033] In the present invention, the preferred silane coupling agent is KH550, and the preferred solvent in step S101 is a mixed solvent consisting of ethanol and deionized water. The preferred mass ratio of ethanol to deionized water in the mixed solvent is (10-15):1.

[0034] In the present invention, the preferred material of the injection needle body is stainless steel or polyimide.

[0035] Furthermore, in order to make the surface of the injection needle body have abundant hydroxyl groups and facilitate the modification of the surface of the injection needle body, the present invention preferably pre-treats the injection needle body according to the following method before surface modification of the injection needle body by a silane coupling agent when the injection needle body is made of stainless steel: S001: After soaking the injection needle body in HCl, ultrasonic treatment was performed in an ethanol bath to obtain an E-stainless steel microneedle; S002: Anodizing the E-stainless steel microneedle in an ethylene glycol-based electrolyte to obtain anodized stainless steel microneedle, which is recorded as EA-stainless steel microneedle; S003: heat-treating the EA-stainless steel microneedle at 500° C. in an inert gas atmosphere to obtain a pre-treated injection needle body.

[0036] When the injection needle body is preferably made of polyimide, the injection needle body is pretreated as follows before the surface of the injection needle body is modified by a silane coupling agent: the injection needle body is pretreated with a NaOH solution at room temperature, rinsed, and dried to obtain a pretreated injection needle body.

[0037] Another object of the present invention is to provide a needle for fundus injection, which is prepared by the method for preparing a needle for fundus injection as described above.

[0038] The fundus injection needle provided by the present invention uses a silane coupling agent to simultaneously graft poly-β-serine and butyl groups onto the surface of the injection needle body during the preparation process to achieve surface modification of the injection needle body, so that the modified fundus injection needle has excellent biocompatibility, improves the therapeutic effect of fundus injection, and improves the comfort of patients.

[0039] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, specific embodiments of the present invention are described in detail below.

[0040] Example 1 This embodiment provides a method for preparing a needle for fundus injection, the method comprising the following steps: S001: The polished stainless steel injection needle body was immersed in HCl (mass concentration 36%, Taixing Meilan Chemical Co., Ltd.) at 60 °C for 2 h to remove the chromium oxide passivation layer, and then rinsed in deionized water and ultrasonically treated in an ethanol bath for 30 min, which was recorded as E-stainless steel microneedle; S002: The E-stainless steel microneedles were anodized in an ethylene glycol-based electrolyte containing 0.1 mol / L ammonium fluoride and 0.3 mol / L deionized water at 50 V for 2.0 h (constant voltage mode); during the anodization process, the electrolyte was stirred at 400 rpm in a room temperature water bath; the stainless steel microneedle strip and the graphite plate were the working electrode and the counter electrode, respectively; during the anodization process, the distance between the counter electrode (graphite plate) and the working electrode (stainless steel microneedle) was kept constant at 30 mm; then the anodized E-stainless steel microneedles were quickly rinsed with ethanol and recorded as EA-stainless steel microneedles; S003: heat treating the EA-stainless steel microneedle at 500°C in an argon atmosphere for 2 h in a tube furnace to obtain a pretreated injection needle body; S1: Surface modification of the injection needle body by silane coupling agent: S11: a silane coupling agent (KH550) and a solvent (ethanol and deionized water in a mass ratio of 10:1) were mixed, stirred for 20 minutes, acetic acid was added, the pH value was adjusted to 5, and then rapidly stirred for 30 minutes to obtain a silane coupling agent solution; S12: placing the pretreated injection needle body in a silane coupling agent solution for ultrasonic treatment for 30 minutes, and then drying it in an oven at 40° C. for 24 hours to obtain a surface-modified injection needle; S2: Preparation of acrylic acid-modified poly-β-serine: S21: A two-necked flat-bottomed flask was equipped with a magnetic stirring bar, and poly-β-serine (1.75 g, about 0.25 mmol), TEA (0.033 mL, 0.25 mmol) and anhydrous THF (25 ml) were added into the two-necked flat-bottomed flask and mixed to obtain a first reaction solution; S22: Add acryloyl chloride (0.02 mL, 0.25 mmol) to anhydrous THF (25 mL) and mix to obtain a second solution; S23: adding the second reaction solution dropwise to the first reaction solution at 0° C. under nitrogen atmosphere, and refluxing the reaction for 24 hours to obtain a reaction mixture; S24: adding the reaction mixture into ethanol, filtering, precipitating, and washing with ethanol three times to obtain acrylic acid-modified poly-β-serine; S3: The surface-modified injection needle is immersed in an aqueous solution of acrylic acid-modified poly-β-serine (the mass concentration of acrylic acid-modified poly-β-serine is 5%) at 60°C for reaction for 6 hours, the injection needle is taken out, and then immersed in a toluene solution of butyl bromide (the mass concentration of butyl bromide is 10%) at 80°C for reaction for 10 hours to obtain a needle for fundus injection.

[0041] Example 2 The difference between this embodiment and embodiment 1 is that step S3 includes the following process: S3: The surface-modified injection needle is immersed in an aqueous solution of acrylic acid-modified poly-β-serine (the mass concentration of acrylic acid-modified poly-β-serine is 15%) at 50°C for 7 hours, the injection needle is taken out, and then immersed in a toluene solution of butyl bromide (the mass concentration of butyl bromide is 30%) at 70°C for 12 hours to obtain a needle for fundus injection.

[0042] Example 3 The difference between this embodiment and embodiment 1 is that step S3 includes the following process: S3: The surface-modified injection needle is immersed in an aqueous solution of acrylic acid-modified poly-β-serine (the mass concentration of acrylic acid-modified poly-β-serine is 10%) at 70°C for reaction for 5 hours, the injection needle is taken out, and then immersed in a toluene solution of butyl bromide (the mass concentration of butyl bromide is 20%) at 90°C for reaction for 8 hours to obtain a needle for fundus injection.

[0043] Example 4 The difference between this embodiment and embodiment 1 is that step S2 includes the following process: S2: Preparation of acrylic acid-modified poly-β-serine: S21: A two-necked flat-bottomed flask was equipped with a magnetic stirring bar, and poly-β-serine (1.75 g, about 0.25 mmol), TEA (0.1 mL, 0.75 mmol) and anhydrous THF (25 ml) were added to the two-necked flat-bottomed flask and mixed to obtain a first reaction solution; S22: Add acryloyl chloride (0.06 mL, 0.75 mmol) to anhydrous THF (35 mL) and mix to obtain a second solution; S23: adding the second reaction solution dropwise to the first reaction solution at 0° C. under nitrogen atmosphere, and refluxing the reaction for 24 hours to obtain a reaction mixture; S24: adding the reaction mixture into ethanol, filtering, precipitating, and washing with ethanol three times to obtain acrylic acid-modified poly-β-serine.

[0044] Example 5 The difference between this embodiment and embodiment 1 is that step S2 includes the following process: S2: Preparation of acrylic acid-modified poly-β-serine: S21: A two-necked flat-bottomed flask was equipped with a magnetic stirring bar, and poly-β-serine (1.75 g, about 0.25 mmol), TEA (0.066 mL, 0.5 mmol) and anhydrous THF (25 ml) were added to the two-necked flat-bottomed flask and mixed to obtain a first reaction solution; S22: Add acryloyl chloride (0.04 mL, 0.5 mmol) to anhydrous THF (30 mL) and mix to obtain a second solution; S23: adding the second reaction solution dropwise to the first reaction solution at 0° C. under nitrogen atmosphere, and refluxing the reaction for 24 hours to obtain a reaction mixture; S24: adding the reaction mixture into ethanol, filtering, precipitating, and washing with ethanol three times to obtain acrylic acid-modified poly-β-serine.

[0045] Example 6 The difference between this embodiment and embodiment 1 is that the injection needle body is made of polyimide, and the injection needle body is pretreated according to the following method: The polyimide injection needle body was pretreated with a NaOH solution (mass concentration of 8%) at room temperature for 1 hour, rinsed with deionized water, and then dried in an oven at 60° C. for 6 hours to obtain a pretreated injection needle body.

[0046] Each comparative example in the present invention is compared with Example 1.

[0047] Comparative Example 1 The fundus injection needle in this comparative example is the injection needle body made of polished stainless steel in Example 1.

[0048] Comparative Example 2 This comparative example provides a method for preparing a needle for fundus injection, the preparation method comprising the following steps: S001: The polished stainless steel injection needle body was immersed in HCl (mass concentration 36%, Taixing Meilan Chemical Co., Ltd.) at 60 °C for 2 h to remove the chromium oxide passivation layer, and then rinsed in deionized water and ultrasonically treated in an ethanol bath for 30 min, which was recorded as E-stainless steel microneedle; S002: The E-stainless steel microneedles were anodized in an ethylene glycol-based electrolyte containing 0.1 mol / L ammonium fluoride and 0.3 mol / L deionized water at 50 V for 2.0 h (constant voltage mode); during the anodization process, the electrolyte was stirred at 400 rpm in a room temperature water bath; the stainless steel microneedle strip and the graphite plate were the working electrode and the counter electrode, respectively; during the anodization process, the distance between the counter electrode (graphite plate) and the working electrode (stainless steel microneedle) was kept constant at 30 mm; then the anodized E-stainless steel microneedles were quickly rinsed with ethanol and recorded as EA-stainless steel microneedles; S003: heat treating the EA-stainless steel microneedle at 500°C in an argon atmosphere for 2 h in a tube furnace to obtain a pretreated injection needle body; S1: Surface modification of the injection needle body by silane coupling agent: S11: a silane coupling agent (KH550) and a solvent (ethanol and deionized water in a mass ratio of 10:1) were mixed, stirred for 20 minutes, acetic acid was added, the pH value was adjusted to 5, and then rapidly stirred for 30 minutes to obtain a silane coupling agent solution; S12: placing the pretreated injection needle body in a silane coupling agent solution for ultrasonic treatment for 30 minutes, and then drying it in an oven at 40° C. for 24 hours to obtain a surface-modified injection needle; S2: Preparation of acrylic acid-modified poly-β-serine: S21: A two-necked flat-bottomed flask was equipped with a magnetic stirring bar, and poly-β-serine (1.75 g, about 0.25 mmol), TEA (0.033 mL, 0.25 mmol) and anhydrous THF (25 ml) were added into the two-necked flat-bottomed flask and mixed to obtain a first reaction solution; S22: Add acryloyl chloride (0.02 mL, 0.25 mmol) to anhydrous THF (25 mL) and mix to obtain a second solution; S23: adding the second reaction solution dropwise to the first reaction solution at 0° C. under nitrogen atmosphere, and refluxing the reaction for 24 hours to obtain a reaction mixture; S24: adding the reaction mixture into ethanol, filtering, precipitating, and washing with ethanol three times to obtain acrylic acid-modified poly-β-serine; S3: The surface-modified injection needle was immersed in an aqueous solution of acrylic acid-modified poly-β-serine (the mass concentration of acrylic acid-modified poly-β-serine was 5%) at 60° C. for 6 hours to obtain a needle for fundus injection.

[0049] Comparative Example 3 This comparative example provides a method for preparing a needle for fundus injection, the preparation method comprising the following steps: S001: The polished stainless steel injection needle body was immersed in HCl (mass concentration 36%, Taixing Meilan Chemical Co., Ltd.) at 60 °C for 2 h to remove the chromium oxide passivation layer, and then rinsed in deionized water and ultrasonically treated in an ethanol bath for 30 min, which was recorded as E-stainless steel microneedle; S002: The E-stainless steel microneedles were anodized in an ethylene glycol-based electrolyte containing 0.1 mol / L ammonium fluoride and 0.3 mol / L deionized water at 50 V for 2.0 h (constant voltage mode); during the anodization process, the electrolyte was stirred at 400 rpm in a room temperature water bath; the stainless steel microneedle strip and the graphite plate were the working electrode and the counter electrode, respectively; during the anodization process, the distance between the counter electrode (graphite plate) and the working electrode (stainless steel microneedle) was kept constant at 30 mm; then the anodized E-stainless steel microneedles were quickly rinsed with ethanol and recorded as EA-stainless steel microneedles; S003: heat treating the EA-stainless steel microneedle at 500°C in an argon atmosphere for 2 h in a tube furnace to obtain a pretreated injection needle body; S1: Surface modification of the injection needle body by silane coupling agent: S11: a silane coupling agent (KH550) and a solvent (ethanol and deionized water in a mass ratio of 10:1) were mixed, stirred for 20 minutes, acetic acid was added, the pH value was adjusted to 5, and then rapidly stirred for 30 minutes to obtain a silane coupling agent solution; S12: placing the pretreated injection needle body in a silane coupling agent solution for ultrasonic treatment for 30 minutes, and then drying it in an oven at 40° C. for 24 hours to obtain a surface-modified injection needle; S2: The surface-modified injection needle is immersed in a toluene solution of butyl bromide (the mass concentration of butyl bromide is 5%) at 80° C. for 10 hours to obtain a needle for fundus injection.

[0050] The performance test of the injection needles prepared in the above embodiments and comparative examples was carried out, and the test method was as follows: 1) Cell viability: Cytotoxicity test (MTT method) was performed according to GB / T 16886.5-2017.

[0051] 2) Anti-protein adhesion performance: Bovine fibrinogen (1 mg / mL, PBS, pH 7.4) and 100% fetal bovine serum (FBS) were used. The injection needles were placed in the protein solution or 100% FBS (both for 3 h, 37°C, 5% CO2, 95% relative humidity). After protein adsorption, they were washed three times with PBS. Then, 1 ml of sodium dodecyl sulfate (SDS) solution (2 wt . %) was added for 30 minutes (37°C) to remove the proteins adsorbed on these injection needles. The amount of protein eluted in the SDS solution was quantified at 578 nm using the BCA protein assay kit.

[0052] 3) Antibacterial properties: 0.1mL concentration is 1×10 8 ~3×10 8 CFU / mL of Staphylococcus aureus solution (PBS buffer) was inoculated on each sample. Each sample was divided into two groups and cultured in a light and dark room for 30 minutes, respectively. Then 0.9 mL of PBS buffer was added to each sample, mixed evenly, and the original bacterial solution and the bacterial solution on the sample were diluted in a centrifuge tube in a gradient of 10 6 10-fold dilution series was prepared. 10 μ The L solution was injected onto a plate containing agar medium and placed in a constant temperature incubator at 37°C for 24 hours. Finally, the colony count was determined, the bacterial survival rate was calculated, and the antibacterial effect was evaluated.

[0053] The test results are shown in Table 1: Table 1 Cell viability (%) Protein adhesion performance (ug / cm2) Bacterial survival rate (%) Example 1 92 0.24 2.4 Example 2 89 0.23 2.5 Example 3 93 0.22 2.6 Example 4 88 0.25 2.3 Example 5 90 0.28 2.7 Example 6 94 0.30 2.8 Comparative Example 1 64 1.38 95.3 Comparative Example 2 55 0.68 92.4 Comparative Example 3 48 1.29 83.6 It can be seen from the data in Table 1 that the injection needles obtained after various treatments in the present invention have excellent biocompatibility, anti-protein adhesion performance and antibacterial performance.

[0054] Based on the above ideal embodiments of the present invention, the relevant staff can make various changes and modifications without departing from the technical concept of the present invention through the above description. The technical scope of the present invention is not limited to the contents of the specification, and its technical scope must be determined according to the scope of the claims.

Claims

1. A method for preparing a needle for fundus injection, characterized in that: The method comprises the following steps: after surface modification of the injection needle body by means of a silane coupling agent, a first soaking reaction is carried out in an acrylic acid-modified poly-β-serine aqueous solution at 50-70° C., and then a second soaking reaction is carried out in a toluene solution of butyl bromide at 70-90° C. to obtain a fundus injection needle.

2. The method for preparing a needle for fundus injection according to claim 1, characterized in that: The acrylic acid-modified poly-β-serine is prepared according to the following method: S21: mixing poly-β-serine, triethylamine and anhydrous tetrahydrofuran to obtain a first reaction solution; S22: mixing acryloyl chloride and anhydrous tetrahydrofuran to obtain a second reaction solution; S23: adding the second reaction solution dropwise to the first reaction solution at 0° C. under an inert atmosphere, and reflux the reaction to obtain a reaction mixture; S24: adding the reaction mixture into ethanol, filtering, precipitating, and washing to obtain acrylic acid-modified poly-β-serine.

3. The method for preparing a needle for fundus injection according to claim 2, characterized in that: The molar ratio of the poly-β-serine to the acryloyl chloride is 1:(1-3).

4. The method for preparing a needle for fundus injection according to any one of claims 1 to 3, characterized in that: Surface modification of the syringe needle body by silane coupling agent includes: S11: After mixing the silane coupling agent and the solvent, an acidic substance is added, and the pH value is adjusted to 5 to obtain a silane coupling agent solution; S12: placing the injection needle body in the silane coupling agent solution for ultrasonic treatment, and then drying to obtain a surface-modified injection needle.

5. The method for preparing a needle for fundus injection according to claim 4, characterized in that: The silane coupling agent is KH550.

6. The method for preparing a needle for fundus injection according to claim 4, characterized in that: The solvent in step S101 is a mixed solvent consisting of ethanol and deionized water.

7. The method for preparing a needle for fundus injection according to claim 4, characterized in that: The injection needle body is made of stainless steel or polyimide.

8. The method for preparing a needle for fundus injection according to claim 7, characterized in that: When the injection needle body is made of stainless steel, the injection needle body is pretreated according to the following method before the surface of the injection needle body is modified by a silane coupling agent: S201: soaking the injection needle body in HCl, and then ultrasonically treating it in an ethanol bath to obtain an E-stainless steel microneedle; S202: Anodizing the E-stainless steel microneedle in an ethylene glycol-based electrolyte to obtain anodized stainless steel microneedle, which is recorded as EA-stainless steel microneedle; S203: heat-treating the EA-stainless steel microneedle at 500° C. in an inert gas atmosphere to obtain a pre-treated injection needle body.

9. The method for preparing a needle for fundus injection according to claim 7, characterized in that: When the injection needle body is made of polyimide, before the surface of the injection needle body is modified by a silane coupling agent, the injection needle body is pretreated according to the following method: the injection needle body is pretreated with a NaOH solution at room temperature, rinsed, and dried to obtain a pretreated injection needle body.

10. A needle for fundus injection, characterized in that: The method is prepared by the method for preparing a needle for fundus injection as described in any one of claims 1 to 9.

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